Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

Imaging characteristics of brain microstructure and cerebral perfusion in Crohn’s disease patients with anxiety: A prospective comparative study

BACKGROUND Anxiety is a common comorbidity in patients with Crohn’s disease(CD).Data on the imaging characteristics of brain microstructure and cerebral perfusion in CD with anxiety are limited.AIM To compare the imaging characteristics of brain microstructure and cerebral perfusion among CD patients with or without anxiety and healthy individuals.METHODS This prospective comparative study enrolled consecutive patients with active CD and healthy individuals who visited the study hospital between January 2022 and January 2023.Anxiety was measured using the Hospital Anxiety and Depression Scale-Anxiety.The imaging characteristics of brain microstructure and cerebral perfusion were measured by diffusion kurtosis imaging and intravoxel incoherent motion.RESULTSA total of 57 participants were enrolled. Among the patients with active CD, 16 had anxiety. Compared withhealthy individuals, patients with active CD demonstrated significantly lower radial kurtosis values in the rightcerebellar region 6, lower axial kurtosis (AK) values in the right insula, left superior temporal gyrus, and rightthalamus, and higher slow and fast apparent diffusion coefficients (ADCslow and ADCfast) in the bilateral frontal lobe,bilateral temporal lobe, and bilateral insular lobe (all P < 0.05). Compared with patients with CD without anxiety,patients with CD and anxiety exhibited significantly higher ADCslow values in the left insular lobe and lower AKvalues in the right insula and right anterior cuneus (all P < 0.05).CONCLUSIONThere are variations in brain microstructure and perfusion among CD patients with/without anxiety and healthyindividuals, suggesting potential use in assessing anxiety-related changes in active CD.

Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury

Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability worldwide.Although PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely unknown.Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH.In this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery.Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage.Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of PTH.Additionally,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying PTH.Moreover,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH.Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.

Cerebral syphilitic gumma misdiagnosed as brain abscess: A case report

BACKGROUND Cerebral syphilitic gumma is a relatively rare clinical disease.Its clinical manifest-ations are non-specific,and the imaging manifestations are similar to other in-tracranial occupying lesions,often misdiagnosed as tumors or abscesses.There are few reports on this disease in the relevant literature.To our knowledge,we have reported the first case of cerebral syphilitic gumma misdiagnosed as a brain abscess.We report this case and provide useful information for clinical doctors on neurosyphilis diseases.CASE SUMMARY We report the case to explore the diagnostic essentials of cerebral syphilitic gumma and attempt to mitigate the rates of misdiagnosis and missed diagnosis by equipping physicians with knowledge of neurosyphilis characteristics.The cli-nical diagnosis and treatment of a patient with cerebral syphilitic gumma were reported.Clinical manifestations,classifications,and diagnostic points were retro-spectively analyzed.The patient was admitted to the hospital with fever and limb weakness.Brain magnetic resonance imaging showed multiple space-occupying lesions and a positive serum Treponema pallidum gelatin agglutination test.The patient was misdiagnosed as having a brain abscess and underwent a craniotomy.A postoperative pathological diagnosis of syphilis gumma was made.The patient improved and was discharged after penicillin anti-syphilis treatment.Follow-up recovery was satisfactory.CONCLUSION Cerebral syphilitic gumma is rare in clinical practice,and it is often misdiagnosed and missed.Clinical diagnosis should be considered in combination with multiple examinations.

Inhibition of the cGAS–STING pathway:contributing to the treatment of cerebral ischemia-reperfusion injury

The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.

Dysfunction of blood-brain barrier in cerebral amyloid angiopathy

Increasing evidence demonstrated that the blood-brain barrier(BBB)was involved in developing cerebral amyloid angiopathy(CAA).The BBB participates in the neurovascular coupling and regulates the transport of substances,which is closely related to neurodegenerative diseases.In CAA,the deposition of amyloid beta(Aβ)in arteries,capillaries,and arterioles of meninges and cerebral cortex results in the destruction of the BBB,chronic inflammatory response,chronic cerebral hypoperfusion,and dysfunction of the neurovascular unit,which eventually leads to neurodegeneration.At the same time,CAA is an age-related disease.Patients with CAA often have some risk factors for cerebrovascular diseases,such as hypertension and diabetes,which can further aggravate the damage to the BBB.Thus,it is of great significance to pay attention to the BBB in the pathogenesis and future intervention targets of CAA.Therefore,this manuscript reviewed the dysfunction of the BBB in CAA.

Revisiting cerebral endothelial cells in Alzheimer’s disease

Alzheimer’s disease(AD)is the most common neurodegenerative disorder characterized by slow and progressive decline of cognitive and memory functions.In only approximately 5%of the cases,AD is familial,as often predisposed by genetic mutations(Hoogmartens et al.,2021),while sporadic AD accounts for approximately 95%of the cases.The amyloid cascade hypothesis is one of the fundamental hypotheses put out to explain AD pathogenesis as dysregulated homeostasis of amyloid-β(Aβ)peptides that leads to the accumulation of Aβplaques in the parenchyma,an anatomical hallmark of AD.

Roles of N-cadherin in cerebral cortical development:cooperation with membrane trafficking and actin cytoskeletal regulation

Cell adhesion plays pivotal roles in the morphogenesis of multicellular organisms.Epithelial cells form several types of cell-to-cell adhesion,including zonula occludens(tight junctions),zonula adhaerens(adherens junctions),and macula adhaerens(desmosomes).Although these adhesion complexes are basically observed only in epithelial cells,cadherins,which are the major cell adhesion molecules of adherens junctions,are expressed in both epithelial and non-epithelial tissues,including neural tissues(Kawauchi,2012).The cadherin superfamily consists of more than 100 members,but classic cadherins.

Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.

Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance

Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.

Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Near-infrared brain functional characteristics of mild cognitive impairment with sleep disorders

BACKGROUND Mild cognitive impairment(MCI)has a high risk of progression to Alzheimer’s disease.The disease is often accompanied by sleep disorders,and whether sleep disorders have an effect on brain function in patients with MCI is unclear.AIM To explore the near-infrared brain function characteristics of MCI with sleep disorders.METHODS A total of 120 patients with MCI(MCI group)and 50 healthy subjects(control group)were selected.All subjects underwent the functional near-infrared spec-troscopy test.Collect baseline data,Mini-Mental State Examination,Montreal Cognitive Assessment scale,fatigue severity scale(FSS)score,sleep parameter,and oxyhemoglobin(Oxy-Hb)concentration and peak time of functional near-infrared spectroscopy test during the task period.The relationship between Oxy-RESULTS Compared with the control group,the FSS score of the MCI group was higher(t=11.310),and the scores of Pittsburgh sleep quality index,sleep time,sleep efficiency,nocturnal sleep disturbance,and daytime dysfunction were higher(Z=-10.518,-10.368,-9.035,-10.661,-10.088).Subjective sleep quality and total sleep time scores were lower(Z=-11.592,-9.924).The sleep efficiency of the MCI group was lower,and the awakening frequency,rem sleep latency period,total sleep time,and oxygen desaturation index were higher(t=5.969,5.829,2.887,3.003,5.937).The Oxy-Hb concentration at T0,T1,and T2 in the MCI group was lower(t=14.940,11.280,5.721),and the peak time was higher(t=18.800,13.350,9.827).In MCI patients,the concentration of Oxy-Hb during T0 was negatively correlated with the scores of Pittsburgh sleep quality index,sleep time,total sleep time,and sleep efficiency(r=-0.611,-0.388,-0.563,-0.356).It was positively correlated with sleep efficiency and total sleep time(r=0.754,0.650),and negatively correlated with oxygen desaturation index(r=-0.561)and FSS score(r=-0.526).All comparisons were P<0.05.CONCLUSION Patients with MCI and sleep disorders have lower near-infrared brain function than normal people,which is related to sleep quality.Clinically,a comprehensive assessment of the near-infrared brain function of patients should be carried out to guide targeted treatment and improve curative effect.

Mimicking aneurysm in a patient with chronic occlusion of the left middle cerebral artery

The chronic occlusion of intracranial arteries generally has no or mild clinical symptoms,and the clinical symptoms of acute cerebral artery occlusion are mostly manifested as severe cerebral infarction symptoms,which often make early diagnosis difficult,thus losing the best treatment opportunity.Once cerebral infarction occurs,the consequences are difficult to recover.This is also an important reason for the high misdiagnosis rate and mortality of this disease.In this paper,the characteristics of the disease were analyzed to provide clinical reference.

Cerebral fat embolism following autologous fat injection in facial reconstruction:A case report

BACKGROUND Autologous fat injection in facial reconstruction is a common cosmetic surgery.Although cerebral fat embolism(CFE)as a complication is rare,it carries serious health risks.CASE SUMMARY We present a case of a 29-year-old female patient who developed acute CFE following facial fat filling surgery.After the surgery,the patient experienced symptoms including headache,nausea,vomiting,and difficulty breathing,which was followed by neurological symptoms such as slurred speech and left-sided weakness.Comprehensive physical examination and auxiliary investigations,including blood tests,head and neck computed tomography angiography,and cranial magnetic resonance diffusion-weighted imaging,were performed upon admission.The clinical diagnosis was acute cerebral embolism following facial fat filling surgery.Treatment included measures to improve cerebral circulation,dehydration for intracranial pressure reduction,nutritional support,and rehabilitation therapy for left limb function.The patient showed a significant improvement in symptoms after 2 weeks of treatment.She recovered left limb muscle strength to grade 5,had clear speech,and experienced complete relief of headache.CONCLUSION Our case highlights the potential occurrence of severe complications in patients undergoing fat injection in facial reconstruction.To prevent these complications,plastic surgeons should enhance their professional knowledge and skills.

A new horizon for neuroscience:terahertz biotechnology in brain research

Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain sciences.In this article,we review the development of terahertz biotechnology and its applications in the field of neuropsychiatry.Available evidence indicates promising prospects for the use of terahertz spectroscopy and terahertz imaging techniques in the diagnosis of amyloid disease,cerebrovascular disease,glioma,psychiatric disease,traumatic brain injury,and myelin deficit.In vitro and animal experiments have also demonstrated the potential therapeutic value of terahertz technology in some neuropsychiatric diseases.Although the precise underlying mechanism of the interactions between terahertz electromagnetic waves and the biosystem is not yet fully understood,the research progress in this field shows great potential for biomedical noninvasive diagnostic and therapeutic applications.However,the biosafety of terahertz radiation requires further exploration regarding its two-sided efficacy in practical applications.This review demonstrates that terahertz biotechnology has the potential to be a promising method in the field of neuropsychiatry based on its unique advantages.

Decoding molecular mechanisms:brain aging and Alzheimer's disease

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.

Engendered nanoparticles for treatment of brain tumors

Brain metastasis and primary glioblastoma multiforme represent the most common and lethal malignant brain tumors.Its median survival time is typically less than a year after diagnosis.One of the major challenges in treating these cancers is the efficiency of the transport of drugs to the central nervous system.The blood-brain barrier is cooperating with advanced stages of malignancy.The blood-brain barrier poses a significant challenge to delivering systemic medications to brain tumors.Nanodrug delivery systems have emerged as promising tools for effectively crossing this barrier.Additionally,the development of smart nanoparticles brings new hope for cancer diagnosis and treatment.These nanoparticles improve drug delivery efficiency,allowing for the creation of targeted and stimuli-responsive delivery methods.This review highlights recent advancements in nanoparticle and smart nanoparticle technologies for brain cancer treatment,exploring the range of nanoparticles under development,their applications,targeting strategies,and the latest progress in enhancing transport across the blood-brain barrier.It also addresses the ongoing challenges and potential benefits of these innovative approaches.